This study aimed to investigate the effects of maternal vitamin D restriction on carbohydrate metabolism and alterations in the pancreas and liver in the F1 and F2 generations. Therefore, we studied the first two generations of offspring (F1 and F2) of Swiss mice from mothers fed one of two diets: SC (standard chow) or VitD− (vitamin D-deficient). Biometric, biochemical and molecular analyses were performed. The VitD-F1 mice had greater body mass (BM) than the SC-F1 mice. The BM changes were accompanied by increased insulin secretion. The VitD-F1 mice had a higher area under the curve in the oral glucose tolerance test and exhibited larger islet diameters than the SC-F1 mice. In addition, the VitD-F1 mice showed marked diffuse hepatic steatosis and higher expression of fatty acid synthase (FAS) protein than the SC animals in either generation or the ViD-F2 mice. Diet accounted for a greater fraction of the total variation for BM, fat pad mass and insulin secretion than generation. Both diet and generation contributed to the variation in steatosis in the liver, islet diameter and expression of FAS. However, interactions between diet and generation were observed only for insulin secretion, steatosis in the liver and FAS expression. In conclusion, these results provide compelling evidence that maternal vitamin D restriction affects the development of the offspring and leads to metabolic alterations accompanied by structural alterations in the liver and pancreas, especially in the F1 generation.
The purpose of this study was to investigate the effects of low-volume exercise training (90 min/wk) and vitamin E supplementation on oxidative stress markers in postmenopausal women. The participants were non-randomly assigned the following four groups: control (C, n=8), vitamin E (S, n=8), exercise (Ex, n=6), or vitamin E and exercise (S+Ex, n=7). The S and S+Ex groups were instructed to take vitamin E (α-tocopherol, 300 mg/d) capsules for 12 wk. The exercise program of Ex and S+Ex groups consisted of walking for a 30-60 min/session 2 d per week for 12 wk. The serum derivatives of reactive oxygen metabolites concentrations were significantly decreased in the Ex, and S+Ex groups after 12 wk compared with the baseline values (three-factor ANOVA, an interaction between exercise and time, p<0.05). Conversely, serum biological antioxidant potential concentrations in the S and Ex groups were significantly higher at 12 wk than at the baseline, but not in the S+Ex group (three-factor ANOVA, an interaction between supplementation, exercise and time, p<0.05). Plasma thioredoxin concentrations in the S, Ex, and S+Ex groups were significantly higher at 12 wk than at the baseline values (three-factor ANOVA, interactions between exercise and time, and between supplementation, exercise and time, p<0.05). Our findings suggest that low-volume physical activity may improve resting oxidative stress status in postmenopausal women.
The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.
Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/HFD group were significantly lower than those in the DW/HFD group (p<0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.
Forty-four female students with a tendency for constipation (mean age, 20.2±3.3 y) were asked to consume 30 g test pickles daily for 2 wk and were divided into 3 groups: viable-cell intake subjects (n=14, 3.0×105 colony-forming units of viable LAB (lactic acid bacteria) cells per sample), dead-cells intake subjects (n=15, viable cells were heat sterilized), and placebo-intake subjects (n=15, LAB removed from the pickles). γ-Aminobutyric acid content of 75.1±3.2 mg per sample was noted, with no marked difference between samples containing viable and dead cells. Natural killer (NK)-cell activity (% specific lysis) in serum from dead-cell intake subjects was 37.5±17.0% before the start of the test-food intake and 47.7±20.1% after intake, indicating statistically significant effects (p<0.01). However, viable-cell intake and placebo intake subjects showed no statistically significant difference. The number of days with bowel movements significantly increased from 3.8±1.5 to 4.9±1.8 d in the dead-cell intake group, whereas a slight change from 4.6±1.5 to 5.1±1.7 d was observed in the viable-cell intake group. Additionally, the feeling of incomplete evacuation fell and a refreshed feeling increased among the subjects with constipation. Thus, marked enhancement of NK-cell activity and improved bowel symptoms were observed in subjects consuming pickles containing dead LAB cells.
Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p=0.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame.
The purpose of this study was to examine the relationship between the zinc nutritional status and the factors associated with serum zinc concentration in the elderly patients in two nursing facilities: body mass index (BMI), the level of care, the grade of bedriddenness, and the grade of cognitive function. The estimations of the hematological constituents, physical index, and dietary survey were made based on the examination carried out of the 26 disabled elderly patients (male 6, female 20, mean age 90±6 y). The results obtained from this study can be summarized as follows: 1) The low activities of daily living (ADL) group showed a low level of serum zinc concentration, although the uptake rate of zinc by subjects was shown to be high when compared to the Dietary Reference Intakes 2010. 2) The high ADL group showed a high level of serum zinc concentration. 3) The results of multiple regression analysis among the serum zinc concentration, the determined serum ingredients, and the physical characteristics showed the significant correlation of serum zinc concentration against the BMI, the level of care, height, Alb and iron values. 4) The BMI, the level of care, the grade of bedriddenness, and the grade of cognitive function of the subjects changed according to the zinc nutritional status. These results suggested that the actual requirements of zinc of the subjects were different according to the BMI, the level of care, the grade of bedriddenness, and the grade of cognitive function.
The objective of this study was to compare the long-term effect of 40-g daily whole bean soy consumption for a period of 18 mo on blood lipid levels of women. A single-system design was used and 90 women randomly selected in peri-urban Qwa-Qwa, South Africa. Measurements included dietary intake (24-h recall), anthropometric (weight and height) and biochemical lipid parameters with venous blood samples. The respondents were divided into a hypercholesterolemic and normo-cholesterolemic (NC) group and data analyses included descriptive statistics and t-tests on SPSS, version 21.0. The results showed that a large percentage (40%) of the women was hypercholesterolemic. The hypercholesterolemic group showed abnormal mean values for all the lipid parameters at baseline whereas the NC group showed total cholesterol (TC) and LDL-cholesterol (LDL-C) values in the normal range, but abnormally low mean HDL-cholesterol (HDL-C) (0.9±0.6) and high mean triglyceride (TG) (2.3±0.8) levels. At follow-up, the hypercholesterolemic group had significantly improved HDL-C (p=0.000), LDL-C (p=0.032) and TG (p=0.000) levels, but with significantly increased TC (p=0.01). A similar trend was observed in the NC group; however, no significantly improved HDL-C or TG values were observed. It can be concluded that dyslipidemia and obesity were prevalent amongst this group of women. The daily consumption of 40 g of whole soybean, had no significant positive effect on TC, but had a beneficial effect on LDL-C in the women in Qwa-Qwa. The HDL : LDL ratio was also improved in the in the hypercholesterolemic group, thus reducing the risk for CVD. The consumption of whole soybean thus had a beneficial effect on the lipid profile of the women in Qwa-Qwa.
It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.
Increased levels of circulating soluble type of E-selectin (sE-selectin), neutrophil counts and blood pressure are associated with the development of cardiovascular diseases (CVD). In this study, we conducted a cross-sectional study of men who participated in health check-ups, and selected those who were not diagnosed with or being treated for metabolic diseases such as diabetes, hypertension and lipid abnormality according to the health check-ups. We measured their basic clinical parameters including blood pressure and neutrophil count, plasma sE-selectin concentration and lifestyle factors, and assessed their interrelations by multivariate linear regression (MLR) analysis. A total of 351 subjects aged 47.5±8.41 (range, 30-64) y were recruited. Significantly correlated with sE-selectin concentration were neutrophil count, diastolic blood pressure (DBP), and systolic blood pressure (SBP) (Pearson's correlation coefficient, 0.194, 0.220 and 0.175, respectively). MLR analysis showed that sE-selectin concentration was independently positively related with DBP and neutrophil count, whereas neutrophil count was positively associated with sE-selectin concentration but not DBP. DBP, but not SBP, was independently positively correlated with sE-selectin concentration but not neutrophil count. These results indicate that circulating sE-selectin concentration may be a biomarker for indicating subsequent development of metabolic diseases, in particular CVD, from a healthy state.
Since the discovery that hepcidin is expressed in the adipose tissue of obese subjects, attention has been increasingly focused on alterations in iron homeostasis that are associated with adiposity. We examined the production of hepcidin, the expression of hepcidin-related genes and the iron content of the adipose tissue in obesity using Swiss mice fed a high-fat diet (HFD). The mice were maintained on a control diet or HFD for 12 or 24 wk, and body weight, adiposity and glucose homeostasis were evaluated. The expression of several genes (hepcidin, TfR1, TfR2, DMT1, FT-heavy, ferroportin, IRP-1, IRP-2 and HIF-1) and the protein expression of hepcidin and IL-6 were quantified. The iron level was assessed using a Prussian blue reaction in paraffin-embedded tissue. After 24 wk on the HFD, we observed increases in the levels of hepcidin in the serum and the visceral adipose tissue. The IL-6 levels also increased in the visceral adipose tissue. Adipocytes isolated from the visceral adipose tissues of lean and obese mice expressed hepcidin at comparable levels; however, isolated macrophages from the stromal vascular fraction expressed higher hepcidin levels. Adipose tissues from obese mice displayed increased tfR2 expression and the presence of iron. Our results indicate that IL-6 and iron may affect the signaling pathways governing hepcidin expression. Thus, the mice fed HFD for 24 wk represent a suitable model for the study of obesity-linked hepcidin alterations. In addition, hepcidin may play local roles in controlling iron availability and interfering with inflammation in adipose tissue.
Miso paste (miso), a fermented soybean food, is popular in Japan and other Asian countries. However, the soybean is known to induce an allergenic response in some individuals. In the present study, we evaluated the allergenicity of various kinds of miso available in Japan. Total proteins were extracted from Amakuti-kome miso, Karakuti-kome miso, Mugi-miso and Mame-miso, and the protein profiles were analyzed. The major protein bands detected in the intact soybean extract were not present in any of the miso samples, which instead showed various low molecular weight protein bands of approximately 10-25 kDa. The existence levels of six major soybean allergens were determined by Western blotting using specific antibodies. We found that the allergen levels varied among miso and allergen types; however, allergen levels were consistently lower in miso than in the soybean extract. We obtained similar results for IgE-ELISA experiments using serum IgE from soybean allergy patients. Taken together, these results indicate that compared to soybean extract, various types of miso contain small quantities of intact soybean allergens. Additionally, several lines of evidence indicated that the allergen levels were exceptionally low in the dark-colored Karakuti-kome miso and Mame-miso, which are produced with relatively long fermentation periods, suggesting that the duration of fermentation might be a key factor in the hypoallergenicity of miso.
Hesperidin (HES) and glucosyl hesperidin (GHES) have antihypertensive effects. In the present study, to clarify the antihypertensive mechanisms, we compared the effects of continuous ingestion of HES and GHES in spontaneously hypertensive rats (SHRs). HES and GHES ingestion for 8 wk significantly prevented hypertension and suppressed the mRNA expression of NADPH oxidase subunits and thromboxane A2 synthase in SHR aortas. Further, hesperetin, a common metabolite of HES and GHES, reduced thromboxane B2 release from SHR aortas. These findings indicate that continuous ingestion of HES and GHES prevents hypertension via regulating the gene expression related to the modulation of vascular tone.
Recently n-3 polyunsaturated fatty acids (PUFAs) have been reported to play protective roles against cardiovascular diseases. Pulmonary thromboembolism (PTE) is one of the critical diseases in the circulatory system. However the relationship between n-3 PUFAs and PTE has not been reported. A total of 144 outpatients of the division of cardiology, including 12 of PTE cases, were enrolled in the present study and serum levels of eicosapentaenoic acid (EPA) and arachidonic acid (AA) were analyzed. We found that the EPA/AA ratio of the patients with PTE (the PTE group) was significantly lower than that of the patients without PTE (the non-PTE group) (p=0.007 for log EPA/log AA ratio). Next, the PTE group was divided into two groups by the presence or absence of malignant carcinoma. The PTE without carcinoma group showed significantly lower EPA/AA ratio than that of the non-PTE group (p=0.002 for log EPA/log AA ratio). However, the PTE with carcinoma group did not show the statistical difference in EPA/AA ratio compared with the non-PTE group (p=0.39). These data indicate that PTE may be associated with a low EPA/AA ratio, although the presence of malignant carcinoma should be taken into account.